Neck pain has become a highly significant source of disability and a global health concern, affecting more than 332 million people worldwide (4.9% prevalence). Data from surveys or cohort studies suggest neck pain is associated with work and type of work exposure: each year, 11-14% of workers are interfered or limited in their activity due to neck pain, and office workers are among those with the highest incidence. As the sedentary trend of modern work persists, without better etiological understanding, effective prevention and control, neck pain will continue to impair the quality of work and life of the working population and pose a tremendous socio- economic burden on society. While the pathogenesis of neck pain is still unclear and believed to be multifactorial in nature, past biomechanical studies have confirmed a central role by the mechanical factors, including neck posture, neck muscle forces, and cervical spine disc loads. What biomechanical studies to date have failed to achieve, however, was a detailed, accurate account of how the neck muscular and skeletal components exactly respond during head-neck activities in vivo and how such responses vary across different individuals. This proposal will take advantage of the state-of-the-art technologies for in vivo biomechanical measurements and in silico (computer-based) musculoskeletal modeling to initiate the development of a new scientific knowledge base along with a set of practical guidelines and tools for better evaluation, recognition, and reduction of te risk of occupational neck pain and disorders. Specifically, we are poised to pursue three aims: Aim 1 will measure in vivo head-neck skeletal kinematics and neck muscle activities during dynamic flexion- extension movements and sustained static exertions; Aim 2 will develop and validate subject-specific head- neck musculoskeletal biomechanical models that can predict neck muscle forces and cervical spine disc loads; Aim 3 will implement model-driven computer simulations to evaluate how work and worker characteristics affect neck muscle forces and cervical spine disc loads and establish practical neck pain prevention/intervention guidelines. Successful accomplishment of these aims will lead to a new biomechanical knowledge base and a digital simulation platform enabling cost-effective, time-efficient design of neck-intensive work, evaluation of preventive or protective means for controlling more targeted mechanical risk factors and reducing the prevalence of occupational neck disorders and injuries.